The object of this research program is to carry out biophysical and biochemical studies on the nucleic acids in order to provide insight concerning the mechanism of their action in biological systems. A central part of this program is to use the information on the recently determined three-dimensional structure of tRNA in order to understand more fully its mode of action in biological systems. X-ray diffraction techniques will be used to solve the structure of both initiator and chain elongating tRNAs. Special emphasis will be placed on the conformation of the anticodon loop in these two types of tRNA. In additon, attempts will be made to co-crystallize tRNA with proteins with which it interacts. The molecular structure of these complexes will be determined and they should provide significant insight into the manner in which proteins recognize nucleic acids. In addition, crystallographic studies will be carried out on other nucleic acid-progein complexes, including a DNA binding protein (gene 5 protein of fd phage) complexed to single-stranded DNA. Attempts will be made to crystallize repressor proteins bound to specific double helical DNA fragments. The three-dimensional structure of oligonucleotides will also be studied. This includes fragments of DNA which may have non-Watson Crick base pairs in them, or thymine dimers. In addition, the structure of DNA fragments will be studied with a variety of chemicals bound to it, including intercalating and non-inercalating antibiotics, as well as helix-binding peptides. The structure of RNA oligomers will also be studied.